This project concerns the functions of the exocrine pancreas. We are particularly interested in the mechanisms of digestive enzyme transport. In addition, we are studying how these processes are regulated. The studies on digestive enzyme secretion include investigations on the intracellular transport of digestive enzymes; the assembly, structure and secretory role of the zymogen granule; and disgestive enzyme transport into and out of cells via non-granular pathways which apparently involve the direct transport of individual macromolecules across cell membranes. The regulation of digestive enzyme synthesis and transport by the end-products of digestion (amino acids, monosaccharides, etc.) is also being examined in order to evaluate their role in the regulation of enzyme secretion and digestion. In addition, studies on pancreatic ion transport investigate the mechanisms involved in ion transport across the major electrolyte- and water-secreting surfaces of the pancreas. A better understanding of normal pancreatic function, particularly at the cellular and subcellular level, is prerequisite for understanding and treating disorders of this gland including acute and chronic pancreatitis, carcinoma of the pancreas, and cystic fibrosis of the pancreas. BIBLIOGRAPHIC REFERENCES: Rossier, M., and S.S. Rothman. Kinetics of Na ion uptake and transcellular transit by the pancreas. Am. J. Physiol. 228:1199-1205, 1975. Rothman, S.S. Enzyme secretion in the absence of zymogen granules. Am. J. Physiol. 228:1834, 1975.